Immune-mediated thrombocytopenia in dogs: Is vaccination a factor?

No statistically significant association between recent vaccination and a diagnosis of presumptive primary immune-mediated thrombocytopenia (IMT) was found in a recent retrospective study that examined 48 dogs presumed to have IMT and 96 control dogs.1

As noted in the study, vaccines often are withheld from dogs with a history of IMT (and other immune-mediated conditions) because of the concern that vaccinations may trigger the immune system and result in recrudescence of that immune-mediated condition.1 These are valid concerns, as there have been reports in the human literature of recent vaccination being associated with idiopathic thrombocytopenic purpura. So in lieu of automatic vaccination (especially in patients with a history of more than one episode of IMT), titers may be submitted to support adequate immunity to those specific infectious diseases.

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If vaccination is deemed necessary, vaccine administration can be staggered throughout the year. Medications or supplements the patient was receiving just before or during the first episode of IMT also should be avoided (when possible) in all future treatment protocols in that patient. All of these precautions may apply to other known immune-mediated conditions as well.

Although a statistically significant relationship between vaccination and IMT was not found in this study, the authors note that one cannot rule out the possibility of an infrequent association between the two or a transient, nonclinical, postvaccination IMT.1 They discuss several important limitations of the study, including a lack of information regarding the number of vaccines in the subject's lifetime, an inherent difficulty of confirming the diagnosis of idiopathic IMT, a small sample size and the study's retrospective nature. So it is difficult to conclude whether recent or cumulative vaccinations may or may not increase the risk of idiopathic IMT.

IMT overview

Thrombocytopenia is either primary (idiopathic) or secondary (a potential cause can be identified; Table 1). Idiopathic IMT is an autoimmune disease usually mediated by immunoglobulins directed against platelet membranes and, theoretically, requires antiplatelet antibody testing for a definitive diagnosis. The source of these antiplatelet antibodies currently has not been identified.

Table 1: Conditions associated with secondary thrombocytopenia in dogs

Because of the limited availability and variable sensitivity and specificity of antiplatelet antibody testing, IMT is typically diagnosed based on clinical and laboratory criteria, exclusion of other disease processes and response to treatment. IMT usually results in a severe thrombocytopenia (< 50,000/μl).

Signs of IMT

Patients with IMT typically present with petechiae (pinpoint hemorrhage), ecchymosis (bruising) or overt hemorrhage (e.g., epistaxis, gingival and intestinal bleeding, prolonged bleeding after injury). Patients may appear clinically normal, or they may be presented as emergencies because of anemia or as a result of bleeding into hollow cavities (e.g., hemothorax, hemoabdomen).

Consider these diagnostic tests if you suspect a patient has IMT: an accurate platelet count, a coagulation profile (e.g., activated clotting time, prothrombin time, partial thromboplastin time), a buccal mucosal bleeding time (to help rule out a platelet function disorder) and a von Willebrand antigen test.

Treatment

In the case of secondary thrombocytopenia, the ideal treatment is to control or eliminate the underlying cause. However, in cases of idiopathic IMT, one or more immunosuppressants are typically used. In some patients with idiopathic IMT, an initial intravenous dose of vincristine or vinblastine may be given. Corticosteroids—specifically prednisolone—are the backbone of immunosuppressive therapy but are associated with a wide range of side effects.

Other drugs are often added for additional immunosuppression in refractory cases and to allow a more rapid taper of the corticosteroids. Table 2 lists some of the more commonly used immunosuppressants used to treat IMT. Use of prednisolone is preferred over prednisone. Prednisolone is the active metabolite of prednisone (does not require conversion by the liver), is more readily absorbed and has more in vivo activity. In fact, some dogs are unable to develop therapeutic serum concentrations of prednisolone when given prednisone.2 This may explain why some patients seem to respond poorly to immunosuppression with prednisone.

Table 2: Immunosuppressants used to treat IMT

If immunosuppression fails to control the IMT, consider splenectomy. Some case reports in the human literature have also described the use of oral melatonin in cases of refractory IMT.3

Dr. Lyman is a graduate of The Ohio State University College of Veterinary Medicine. He completed a formal internship at the Animal Medical Center in New York City. Lyman is a co-author of chapters in the 2000 editions of Kirk's Current Veterinary Therapy XIII and Quick Reference to Veterinary Medicine.

Dr. Runde is a graduate of the University of Pennsylvania School of Veterinary Medicine. He completed an internship at Hollywood Animal Hospital. He is an associate veterinarian at the Animal Emergency and Referral Center in Ft. Pierce, Fla.

References

1. Huang AA, Moore GE, Scott-Moncrieff JC. Idiopathic immune-mediated thrombocytopenia and recent vaccination in dogs. J Vet Intern Med 2012;26(1):142-148.

2. Boothe DM. Small animal clinical pharmacology and therapeutics. 2nd ed. St. Louis, Mo: Elsevier Saunders, 2012.

3. Todisco M, Rossi N. Melatonin for refractory idiopathic thrombocytopenic purpura: a report of 3 cases. Am J Ther 2002;9(6):524-526.